Lyophilized ophthalmologic patches as novel corneal drug formulations using a semi-solid extrusion 3D printer.

3D printing technology is a novel and practical approach for producing unique and complex industrial and medical objects. In the pharmaceutical field, the approval of 3D printed tablets by the US Food and Drug Administration has led to other 3D printed drug formulations and dosage forms being proposed and investigated. Here, we report novel ophthalmologic patches for controlled drug release fabricated using a semi-solid material extrusion-type 3D printer. The patch-shaped objects were 3D printed using hydrogel-based printer inks composed of hypromellose (HPMC), sugar alcohols (mannitol, xylitol), and drugs, then freeze-dried. The viscous properties of the printer inks and patches were dependent on the HPMC and sugar alcohol concentrations. Then, the physical properties, surface structure, water uptake, antimicrobial activity, and drug release profile of lyophilized patches were characterized. Lyophilized ophthalmologic patches with different dosages and patterns were fabricated as models of personalized treatments prepared in hospitals. Then, ophthalmologic patches containing multiple drugs were fabricated using commercially available eye drop formulations. The current study indicates that 3D printing is applicable to producing novel dosage forms because its high flexibility allows the preparation of patient-tailored dosages in a clinical setting.

3D printing of gummy drug formulations composed of gelatin and an HPMC-based hydrogel for pediatric use.

The 3D printing of drug formulations is a promising method for preparing tailored medicines following the approval of 3D printed tablets by the US FDA in 2015. Appropriate dosage forms for pediatric patients are deficient because drugs have been developed for mainly adult patients. Here, we fabricated gummy drug formulations for pediatric patients using a 3D bioprinter compatible with semi-solid materials such as hydrogels and pastes. The gummy drug formulations were composed of gelatin, HPMC, reduced syrup, water and the antiepileptic drug lamotrigine. The formulations were extruded from the nozzle of the 3D bioprinter under air pressure and laminated from the bottom in a layer-by-layer process. The incorporation of HPMC aided smooth printing at room temperature, and gelatin and HPMC affected the viscosity of the drug formulation and the printability of the formulations. The strength of the gummy formulations was remarkably influenced by the gelatin concentration. Dissolution tests showed 85% drug release within 15 min from most formulations. The results suggest that 3D printing is an effective method for preparing gummy drug formulations with various shapes in different colors, and that the methodology may improve drug adherence of pediatric patients in future clinical settings.

Lithic technology, chronology, and marine shells from Wadi Aghar, southern Jordan, and Initial Upper Paleolithic behaviors in the southern inland Levant.

The Initial Upper Paleolithic (IUP) temporally overlaps with the range expansion of Homo sapiens populations in various parts of Eurasia and is often considered a key archaeological phase for investigating behavioral changes from the Middle Paleolithic. This paper reports upon new data from IUP occupations at Wadi Aghar, a rock shelter site in the southern Levant. In combining the results of radiometric dates and lithic analyses, we clarify the chronological and cultural position of Wadi Aghar assemblages in the Levantine IUP. As for the records about mobility, on-site activities, and resource procurement behaviors, we present analyses of lithic use-wear, tool-type composition, soil micromorphology, and marine shells. The lithic analyses and the optically stimulated luminescence (and subsidiary radiocarbon) dating of the Wadi Aghar materials suggest their chronocultural position in the IUP (45-40 ka for Layers C-D1; 39-36 ka for Layer B; possibly 50 ka for Layer D2), providing the southernmost location for the IUP in Eurasia. In the Levant, Wadi Aghar represents one of the few IUP sites in the inland areas. The results also indicate that the timing and technological sequences from the IUP to the following bladelet industries differed between the inland and coastal zones, likely reflecting geographically variable adaptive behaviors and/or cultural transmissions. One of the behavioral characteristics of IUP foragers at Wadi Aghar is the procurement of remote resources, represented by the transportation of marine shells from the Red Sea: Canarium fusiforme and Canarium cf. mutabile. Whether it was a direct procurement with increased mobility or a result of intergroup exchanges, it was not part of behavioral repertoires during the late MP in the same area. This can be understood as the expansion of resource procurement range, functioning as additional buffers from risk in the semiarid environments in the inland Levant.